DOCSLIB.ORG

ZC3H12D Is a Prognostic Biomarker Associated with Immune Cell Infiltration in Lung Adenocarcinoma

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ZC3H12D Is a Prognostic Biomarker Associated with Immune Cell Infiltration in Lung Adenocarcinoma 6142 Original Article ZC3H12D is a prognostic biomarker associated with immune cell infiltration in lung adenocarcinoma Wangang Gong1,2,3, Wumin Dai1,2,3, Haibin Wei1,2,3, Yongyi Chen1,2,3, Zhiguo Zheng1,2,3 1Institute of Cancer and Basic Medical (ICBM), Chinese Academy of Sciences, Hangzhou, China; 2Zhejiang Cancer Research Institute, Cancer Hospital of University of Chinese Academy of Sciences, Hangzhou, China; 3Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, China Contributions: (I) Conception and design: Z Zheng; (II) Administrative support: Z Zheng; (III) Provision of study materials or patients: W Dai, Y Chen; (IV) Collection and assembly of data: W Gong, H Wei; (V) Data analysis and interpretation: W Gong; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Zhiguo Zheng, PhD. Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, 1# Banshan Road, Hangzhou 310022, China. Email: [email protected]. Background: ZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear. Methods: The expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan–Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining. Results: The combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues. Conclusions: These findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD. Keywords: Bioinformatics analysis; lung adenocarcinoma (LUAD); infiltration of immune cells; ZC3H12D Submitted Mar 12, 2020. Accepted for publication Aug 05, 2020. doi: 10.21037/tcr-20-1465 View this article at: http://dx.doi.org/10.21037/tcr-20-1465 © Translational Cancer Research. All rights reserved. Transl Cancer Res 2020;9(10):6128-6142 | http://dx.doi.org/10.21037/tcr-20-1465 Translational Cancer Research, Vol 9, No 10 October 2020 6129 Introduction carcinoma have a good prognosis (14). Interestingly, members of the ZC3H12 family also provide a local Primary lung cancer is one of the malignancies associated inflammatory environment for tumor development. For with the highest morbidity and mortality worldwide, example, ZC3H12A degrades transcripts of angiogenic especially in China (1). Non-small cell lung cancer factors secreted by cells (VEGF, IL-8, and IL-6) and (NSCLC) is the main pathologic type of lung cancer, downregulation of ZC3H12A induces tumor angiogenesis accounting for approximately 80% of all lung cancers. in renal cell carcinoma endothelial cells (8). Recently, Lung adenocarcinoma (LUAD) is the most common form ZC3H12D has been considered to be a new negative of NSCLC, accounting for more than 50% of cases (2). feedback regulator of Toll-like receptor (TLR) signaling The prognosis of LUAD is poor, with a 5-year survival and macrophage activation. Overexpression of ZC3H12D rate of 4–17% (3). Immunotherapy is a new method for significantly inhibits JNK, ERK, and NF-κB signal the treatment of LUAD, and has achieved unprecedented transduction and macrophage inflammation induced by results in patients with advanced LUAD. However, there TLR2 and TLR4 activation (13). However, the mechanism is a wide range of challenges in clinical application, such as of ZC3H12 family members in LUAD progression and the lack of biomarkers that can effectively predict efficacy, tumor immunology has not been established. prognosis, and treatment-related adverse reactions (4). In this study we used multiple databases to analyze the In addition, a number of studies have shown that tumor- level of expression and prognosis of different ZC3H12 infiltrating lymphocytes, such as tumor-associated macrophages family proteins in patients with LUAD. We also used the (TAM) and tumor-infiltrating neutrophils (TINs), affect the tumor immune research evaluation resource (TIMER) to prognosis and efficacy of immunotherapy (5). Therefore, analyze the correlation between ZC3H12D and LUAD the identification of prognostic biomarkers and new immune cell infiltration to determine the prognostic value immune-related therapeutic targets has enormous potential of ZC3H12D in LUAD and its interaction with tumor in the treatment for LUAD. immune potential. ZC3H12 is a newly discovered zinc finger protein family of the CCCH type, which consists of four ZC3H12A-D members (6). The ZC3H12 protein family, also known Methods as MCPIP, is an endonuclease that degrades mRNA UALCAN data analysis transcripts by recognizing the stem-loop structure at the end of mRNA 3'UTR (7). ZC3H12 family proteins UALCAN (http://ualcan.path.uab.edu) is an easy-to-use are abnormally expressed in a variety of tumors, and interactive portal for in-depth analysis of TCGA gene participate in the development and progression of tumors, expression data. UALCAN can be used to analyze the thus affecting the prognosis. It has been reported that the relative expression of genes in different tumor types and expression of ZC3H12A is down-regulated in breast cancer, grades, and to evaluate the impact of gene expression and neuroblastomas, and renal clear cell carcinomas, and low clinicopathologic features on patient survival. In addition, expression of ZC3H12A is related to tumor grade and poor additional information about the selected gene/target is prognosis for breast cancer (8,9). Studies have shown that provided through connection with HPRD, GeneCards, the expression of ZC3H12C in colon cancer is lower than Pubmed, TargetScan, Human protein atlas, DRUGBANK, normal colon tissues, while overexpression of ZC3H12C Open targets and GTEx. In this study, UALCAN inhibits the migration of colon cancer cells (10). ZC3H12D database was used for the analysis of the expression of was originally considered to be a tumor suppressor, and ZC3H12 family genes in primary LUAD patients and the has also been referred to as p34, MCPIP4, and TFL (11). investigation of the correlation between the ZC3H12 family Recent studies have shown that ZC3H12D reduces the members and the survival of patients. global ubiquitin of cellular proteins, and polyubiquitin plays a key role in promoting the tumor cell proliferation and Kaplan-Meier plotter database analysis survival signal pathway (12,13). It has also been reported that ZC3H12D is highly expressed in human endometrial Kaplan-Meier Plotter analysis was used to assess how carcinoma, but not expressed or weakly expressed in normal 10,461 cancer samples impacted 54,675 genes on survival. tissues, the patients with high expression of endometrial These samples included 5,143 breast, 1,816 ovarian, 2,437 © Translational Cancer Research. All rights reserved. Transl Cancer Res 2020;9(10):6128-6142 | http://dx.doi.org/10.21037/tcr-20-1465 6130 Gong et al. ZC3H12D is a prognostic biomarker in LUAD lung, and 1,065 gastric cancer samples on the HGU133 cistrome.shinyapps.io/timer/). TIMER used the previously Plus 2.0 array. The average follow-up time was 69, 40, 49 published deconvolution statistical method to infer the and 33 months, respectively (15). Kaplan-Meier Plotter abundance of tumor-infiltrating immune cells from gene (http://kmplot.com/analysis/) was used to analyze the expression profiles. The TIMER database included 10,897 relationship between the expression of ZC3H12 family samples from 32 cancer types from The Cancer Genome genes and the survival of LUAD. The hazard ratio (HR) Atlas (TCGA) to estimate the abundance of immune with 95% confidence intervals and log-rank P-value were infiltration. We analyzed the correlation between the also computed. expression of ZC3H12 family genes and the abundance of immune infiltrating cells (including B cells, CD4+T cells, CD8+T cells, neutrophils, macrophages, and dendritic GEPIA was used to verify the correlation between ZC3H12 cells) through a gene module. Gene expression against family genes and LUAD survival tumor purity is displayed on the left-most panel (18). In Gene Expression Profiling Interactive Analysis
Load more

Recommended publications
  • Doctoral Thesis Genetics of Male Infertility
    DOCTORAL THESIS GENETICS OF MALE INFERTILITY: MOLECULAR STUDY OF NON-SYNDROMIC CRYPTORCHIDISM AND SPERMATOGENIC IMPAIRMENT Deborah Grazia Lo Giacco November 2013 Genetics of male infertility: molecular study of non-syndromic cryptorchidism and spermatogenic impairment Thesis presented by Deborah Grazia Lo Giacco To fulfil the PhD degree at Universitat Autònoma de Barcelona Thesis realized under the direction of Dr. Elisabet Ars Criach and Prof. Csilla Krausz at the laboratory of Molecular Biology of Fundació Puigvert, Barcelona Thesis ascribed to the Department of Cellular Biology, Physiology and Immunology, Medicine School of Universitat Autònoma de Barcelona PhD in Cellular Biology Dr. Elisabet Ars Criach Prof. Csilla Krausz Dr. Carme Nogués Sanmiquel Director of the thesis Director of the thesis Tutor of the thesis Deborah Grazia Lo Giacco Ph.D Candidate A mis padres Agradecimientos Esta tesis es un esfuerzo en el cual, directa o indirectamente, han participado varias personas, leyendo, opinando, corrigiendo, teniéndo paciencia, dando ánimo, acompañando en los momentos de crisis y en los momentos de felicidad. Antes de todo quisiera agradecer a mis directoras de tesis, la Dra Csilla Krausz y la Dra Elisabet Ars, por su dedicación costante y continua a este trabajo de investigación y por sus observaciones y siempre acertados consejos. Gracias por haber sido mentores y amigas, gracias por transmitirme vuestro entusiasmo y por todo lo que he aprendido de vosotras. Mi más profundo agradecimiento a la Sra Esperança Marti por haber creído en el valor de nuestro trabajo y haber hecho que fuera posible. Quisiera agradecer al Dr. Eduard Ruiz-Castañé por su apoyo y ayuda constante, y a todos los médicos del Servicio de Andrología: Dr.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Mir‑128‑3P Serves As an Oncogenic Microrna in Osteosarcoma Cells by Downregulating ZC3H12D
    ONCOLOGY LETTERS 21: 152, 2021 miR‑128‑3p serves as an oncogenic microRNA in osteosarcoma cells by downregulating ZC3H12D MAOSHU ZHU1*, YULONG WU2*, ZHAOWEI WANG3, MINGHUA LIN4, BIN SU5, CHUNYANG LI6, FULONG LIANG7 and XINJIANG CHEN6 Departments of 1Central Laboratory, 2Urinary Surgery, 3Gynecology, 4Pathology, 5Pharmacy, 6Orthopedics and 7Neurology, The Fifth Hospital of Xiamen, Xiang'an, Xiamen, Fujian 361000, P.R. China Received August 30, 2019; Accepted November 24, 2020 DOI: 10.3892/ol.2020.12413 Abstract. Osteosarcoma is the second leading cause of miR‑128‑3p‑mediated molecular pathway and how it is associ‑ cancer‑associated mortality worldwide in children and ated with osteosarcoma development. adolescents. ZC3H12D has been shown to negatively regulate Toll‑like receptor signaling and serves as a possible tumor Introduction suppressor gene. MicroRNAs (miRNAs/miRs) are known to play an important role in the proliferation of human osteo‑ As the most commonly occurring primary malignant bone sarcoma cells. However, whether miRNAs can affect tumor tumor, osteosarcoma accounts for >10% of all solid tumors development by regulating the expression of ZC3H12D has worldwide (1‑3). Osteosarcoma is the second leading cause of not yet been investigated. The aim of the present study was cancer‑associated mortality worldwide and primarily affects to investigate the role of miR128‑3p in regulating ZC3H12D young individuals, including children and adolescents (4,5). expression, as well as its function in tumor cell proliferation, Owing to advancements in surgical technology and combined apoptosis, and metastasis. Reverse transcription‑quantitative therapeutic strategies, the 5‑year overall survival rate of osteo‑ PCR, western blotting and dual luciferase reporter assays were sarcoma has increased to 60‑70% (6).
    [Show full text]
  • Binding Specificities of Human RNA Binding Proteins Towards Structured
    bioRxiv preprint doi: https://doi.org/10.1101/317909; this version posted March 1, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Binding specificities of human RNA binding proteins towards structured and linear 2 RNA sequences 3 4 Arttu Jolma1,#, Jilin Zhang1,#, Estefania Mondragón4,#, Teemu Kivioja2, Yimeng Yin1, 5 Fangjie Zhu1, Quaid Morris5,6,7,8, Timothy R. Hughes5,6, Louis James Maher III4 and Jussi 6 Taipale1,2,3,* 7 8 9 AUTHOR AFFILIATIONS 10 11 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden 12 2Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland 13 3Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom 14 4Department of Biochemistry and Molecular Biology and Mayo Clinic Graduate School of 15 Biomedical Sciences, Mayo Clinic College of Medicine and Science, Rochester, USA 16 5Department of Molecular Genetics, University of Toronto, Toronto, Canada 17 6Donnelly Centre, University of Toronto, Toronto, Canada 18 7Edward S Rogers Sr Department of Electrical and Computer Engineering, University of 19 Toronto, Toronto, Canada 20 8Department of Computer Science, University of Toronto, Toronto, Canada 21 #Authors contributed equally 22 *Correspondence: [email protected] 23 24 25 SUMMARY 26 27 Sequence specific RNA-binding proteins (RBPs) control many important 28 processes affecting gene expression. They regulate RNA metabolism at multiple 29 levels, by affecting splicing of nascent transcripts, RNA folding, base modification, 30 transport, localization, translation and stability. Despite their central role in most 31 aspects of RNA metabolism and function, most RBP binding specificities remain 32 unknown or incompletely defined.
    [Show full text]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • The Roles of Malt1 in Nf-Κb Activation and Solid Tumor Progression
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2016 THE ROLES OF MALT1 IN NF-κB ACTIVATION AND SOLID TUMOR PROGRESSION Deng Pan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Animal Diseases Commons, Animals Commons, Biochemistry Commons, Cancer Biology Commons, Cell Biology Commons, Disease Modeling Commons, Molecular Biology Commons, Molecular Genetics Commons, and the Oncology Commons Recommended Citation Pan, Deng, "THE ROLES OF MALT1 IN NF-κB ACTIVATION AND SOLID TUMOR PROGRESSION" (2016). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 651. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/651 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. THE ROLES OF MALT1 IN NF-κB ACTIVATION AND SOLID TUMOR PROGRESSION by Deng Pan, B.S. APPROVED: ______________________________ Xin Lin, Ph.D. , Advisory Professor ______________________________ Paul Chiao, Ph.D. ______________________________ Dos Sarbassov, Ph.D. ______________________________ M. James You, M.D., Ph.D. ______________________________ Chengming Zhu, Ph.D.
    [Show full text]
  • Regnase-1, a Rapid Response Ribonuclease Regulating Inflammation and Stress Responses
    Cellular & Molecular Immunology (2017) 14, 412–422 & 2017 CSI and USTC All rights reserved 2042-0226/17 $32.00 www.nature.com/cmi REVIEW Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses Renfang Mao1, Riyun Yang1, Xia Chen1, Edward W Harhaj2, Xiaoying Wang3 and Yihui Fan1,3 RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage. The major function of Regnase-1 is promoting mRNA decay via its ribonuclease activity by specifically targeting a subset of genes in different cell types. In monocytes, Regnase-1 downregulates IL-6 and IL-12B mRNAs, thus mitigating inflammation, whereas in T cells, it restricts T-cell activation by targeting c-Rel, Ox40 and Il-2 transcripts. In cancer cells, Regnase-1 promotes apoptosis by inhibiting anti-apoptotic genes including Bcl2L1, Bcl2A1, RelB and Bcl3. Together with up-frameshift protein-1 (UPF1), Regnase-1 specifically cleaves mRNAs that are active during translation by recognizing a stem-loop (SL) structure within the 3′UTRs of these genes in endoplasmic reticulum-bound ribosomes. Through this mechanism, Regnase-1 rapidly shapes mRNA profiles and associated protein expression, restricts inflammation and maintains immune homeostasis. Dysregulation of Regnase-1 has been described in a multitude of pathological states including autoimmune diseases, cancer and cardiovascular diseases.
    [Show full text]
  • A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker
    Hindawi Publishing Corporation Case Reports in Genetics Volume 2014, Article ID 597314, 5 pages http://dx.doi.org/10.1155/2014/597314 Case Report A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker Roberto L. P. Mazzaschi,1 Juliet Taylor,2 Stephen P. Robertson,3 Donald R. Love,1,4 and Alice M. George1 1 Diagnostic Genetics, LabPlus, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand 2 Genetic Health Service New Zealand-Northern Hub, Auckland City Hospital, Private Bag 92024, Auckland 1142, New Zealand 3 Department of Paediatrics and Child Health, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand 4 School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand Correspondence should be addressed to Alice M. George; [email protected] Received 31 December 2013; Accepted 5 February 2014; Published 17 March 2014 Academic Editors: M. Fenger, G. Vogt, and X. Wang Copyright © 2014 Roberto L. P. Mazzaschi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A skin sample from a 17-year-old female was received for routine karyotyping with a set of clinical features including clonic seizures, cardiomyopathy, hepatic adenomas, and skeletal dysplasia. Conventional karyotyping revealed a mosaic Turner syndrome karyotype with a cell line containing a small marker of X chromosome origin. This was later confirmed on peripheral blood cultures by conventional G-banding, fluorescence in situ hybridisation and microarray analysis.
    [Show full text]
  • 2842-2852-Microrna-Mrna and P-P Interaction Analysis in Pancreatic
    Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 2842-2852 Integrative microRNA-mRNA and protein-protein interaction analysis in pancreatic neuroendocrine tumors H.-Q. ZHOU 1,2 , Q.-C. CHEN 2, Z.-T. QIU 2, W.-L. TAN 1, C.-Q. MO 3, S.-W. GAO 1 1Department of Anesthesia, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Chin a 2Sun Yat-sen University School of Medicine, Guangzhou, China 3Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Abstract. – OBJECTIVE : Pancreatic neuroen - Key Words: docrine tumors are relatively rare pancreatic microRNA, mRNA, Pancreatic neuroendocrine tu - neoplasms over the world. Investigations of the mors, Protein-protein interaction network. molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulato - ry processes underlying pancreatic neuroen - Introduction docrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of Pancreatic neuroendocrine tumors (PNETs), GSE43796 were downloaded, including 6 sam - also called islet cell tumors, are relatively rare ples with pancreatic neuroendocrine tumors and pancreatic neoplasms, arising from the endocrine 5 healthy samples. First, the Limma package was tissues rather than glandular epithelium of the utilized to distinguish the differentially ex - pancreas. With secreting a variety of peptide hor - pressed messenger RNA and microRNA sepa - mones, PNETs are terminologically divided as rately. Then we used microRNA Walk databases to predict the target genes of the differentially insulinoma, gastrinoma, glucagonoma, somato - expressed microRNAs (DE-microRNAs), and se - statinoma and vasoactive intestinal peptide tu - lected differentially expressed target genes mors (VIPoma), resulting in numbers of clinical whose expression was reversely correlated with syndromes.
    [Show full text]
  • An Auto-Regulatory Module Controls Fat Metabolism in Caenorhabditis
    An auto-regulatory module controls fat metabolism in Caenorhabditis elegans Inauguraldissertation zur Erlangung der Würde einer Doktorin der Philosophie vorgelegt der Philosophisch-Naturwisschenschaftlichen Fakultät der Universität Basel von Cornelia Habacher aus Österreich Basel, 2018 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Genemigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von: Prof. Dr. Michael Hall Dr. Rafal Ciosk Dr. Hugo Aguilaniu Basel, den 23. Mai 2017 Prof. Dr. Martin Spiess (Dekan der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel) 2 TABLE OF CONTENTS SUMMARY .........................................................................................................................................4 1. INTRODUCTION ..............................................................................................................................5 1.1 Fat metabolism in Caenorhabditis elegans ......................................................................................... 5 1.1.1 Absorption of nutrients ................................................................................................................ 6 1.1.2 Lipid composition and fat accumulation ...................................................................................... 8 1.1.3 Lipid degradation ......................................................................................................................... 9 1.1.4 Signaling pathways regulating lipid
    [Show full text]
  • A Temporally Controlled Sequence of X-Chromosome Inactivation and Reactivation Defines Female Mouse in Vitro Germ Cells with Meiotic Potential
    bioRxiv preprint doi: https://doi.org/10.1101/2021.08.11.455976; this version posted August 11, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential Jacqueline Severino1†, Moritz Bauer1,9†, Tom Mattimoe1, Niccolò Arecco1, Luca Cozzuto1, Patricia Lorden2, Norio Hamada3, Yoshiaki Nosaka4,5,6, So Nagaoka4,5,6, Holger Heyn2, Katsuhiko Hayashi7, Mitinori Saitou4,5,6 and Bernhard Payer1,8* Abstract The early mammalian germ cell lineage is characterized by extensive epigenetic reprogramming, which is required for the maturation into functional eggs and sperm. In particular, the epigenome needs to be reset before parental marks can be established and then transmitted to the next generation. In the female germ line, reactivation of the inactive X- chromosome is one of the most prominent epigenetic reprogramming events, and despite its scale involving an entire chromosome affecting hundreds of genes, very little is known about its kinetics and biological function. Here we investigate X-chromosome inactivation and reactivation dynamics by employing a tailor-made in vitro system to visualize the X-status during differentiation of primordial germ cell-like cells (PGCLCs) from female mouse embryonic stem cells (ESCs). We find that the degree of X-inactivation in PGCLCs is moderate when compared to somatic cells and characterized by a large number of genes escaping full inactivation.
    [Show full text]
  • Patterns of Molecular Evolution of an Avian Neo-Sex Chromosome
    Patterns of Molecular Evolution of an Avian Neo-sex Chromosome Irene Pala,*,1 Dennis Hasselquist,1 Staffan Bensch,1 and Bengt Hansson*,1 1Molecular Ecology and Evolution Lab, Department of Biology, Lund University, Lund, Sweden *Corresponding author: E-mail: [email protected]; [email protected]. Associate editor: Yoko Satta Abstract Newer parts of sex chromosomes, neo-sex chromosomes, offer unique possibilities for studying gene degeneration and sequence evolution in response to loss of recombination and population size decrease. We have recently described a neo-sex chromosome Downloaded from https://academic.oup.com/mbe/article/29/12/3741/1005710 by guest on 28 September 2021 system in Sylvioidea passerines that has resulted from a fusion between the first half (10 Mb) of chromosome 4a and the ancestral Research article sex chromosomes. In this study, we report the results of molecular analyses of neo-Z and neo-W gametologs and intronic parts of neo-Z and autosomal genes on the second half of chromosome 4a in three species within different Sylvioidea lineages (Acrocephalidea, Timaliidae, and Alaudidae). In line with hypotheses of neo-sex chromosome evolution, we observe 1) lower genetic diversity of neo-Z genes compared with autosomal genes, 2) moderate synonymous and weak nonsynonymous sequence divergence between neo-Z and neo-W gametologs, and 3) lower GC content on neo-W than neo-Z gametologs. Phylogenetic reconstruction of eight neo-Z and neo-W gametologs suggests that recombination continued after the split of Alaudidae from the rest of the Sylvioidea lineages (i.e., after 42.2 Ma) and with some exceptions also after the split of Acrocephalidea and Timaliidae (i.e., after 39.4 Ma).
    [Show full text]